Bacterial Biomarker

Abstract

The invention relates to bacterial compositions useful in the treatment of cancer. In particular, the compositions can be used as a co-therapy with an immune checkpoint therapy. The invention also relates to methods for identifying a subject that will respond to therapy with an immune checkpoint inhibitor comprising determining the abundance of bacteria in a biological sample from said subject.

1 - 16 . (canceled) 
     
     
         17 . A composition comprising an isolated faecal sample obtained from one or several individual(s) wherein said faecal sample has an abundance of one or more bacteria selected from Table 1 and wherein the presence or abundance of one or more bacteria is associated with a response to cancer with a checkpoint inhibitor therapy. 
     
     
         18 . The composition of  claim 17  wherein the composition is lyophilized. 
     
     
         19 . The composition of  claim 17  wherein the one or more bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         20 . The composition of  claim 17  wherein the faecal sample has been shown to be abundant in least 2, 3, 4, 5, 6, 7, 8, 9, 1, 11, 12, 13, 14 or 15 different bacterial species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         21 . The composition of  claim 17  wherein the composition is provided for oral administration, optionally in the form of a capsule, tablet or liquid. 
     
     
         22 . The composition of  claim 17  wherein immune checkpoint inhibitor inhibits PD-1, PDL-1, PDL-2, TIM-3, TIGIT, LAG-3 or CTLA-4 activity. 
     
     
         23 . A composition comprising an isolated faecal sample that has been supplemented with one or more bacteria selected from Table 1 or with a faecal sample obtained from a donor wherein the faecal sample has an abundance of one or more bacteria selected from Table 1. 
     
     
         24 . The composition of  claim 23  wherein the composition is lyophilised. 
     
     
         25 . The composition of  claim 23  wherein the one or more bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         26 . The composition of  claim 23  wherein the faecal sample has been shown to be abundant in least 2, 3, 4, 5, 6, 7, 8, 9, 1, 11, 12, 13, 14 or 15 different bacterial species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         27 . The composition of  claim 23  wherein the composition is provided for oral administration, optionally in the form of a capsule, tablet or liquid. 
     
     
         28 . A method for identifying a faecal donor comprising assessing a faecal sample of a subject for the presence of one or more bacteria associated with a response to cancer when a patient is treated with a checkpoint inhibitor wherein said method comprises identifying the faecal donor based on the presence and/or abundance of one or more bacteria selected from Table 1. 
     
     
         29 . The method of  claim 28  wherein said subject is a healthy subject or cancer patient. 
     
     
         30 . The method of  claim 28 , comprising obtaining a faecal sample from a donor. 
     
     
         31 . The method of  claim 28 , wherein said method comprises selecting the donor as a donor for bacteriotherapy purposes if one or more of the bacteria selected from Table 1 is present above a predetermined threshold. 
     
     
         32 . The method of  claim 28  wherein said method comprises selecting the donor as a donor for bacteriotherapy purposes if one or more of the bacteria is present above a predetermined threshold and wherein the predetermined threshold is based on the average abundance of the one or more bacteria in the faecal samples obtained from a donor population and wherein a higher than average abundance indicates that the faeces are suitable for FMT therapy. 
     
     
         33 . The method of  claim 28  wherein the bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         34 . The method of  claim 28  wherein said method comprises identifying the faecal donor based on the presence and/or abundance of at least 2, 3, 4, 5, 6, 7, 8, 9, 1, 11, 12, 13, 14 or 15 different species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         35 . The method of  claim 28  wherein said checkpoint inhibitor inhibits PD-1, PDL-1, PDL-2, TIM-3, TIGIT, LAG-3 or CTLA-4 activity. 
     
     
         36 . A method for treating a faecal transplant prior to administration to a subject comprising supplementing the faecal transplant with a faecal sample obtained from a donor by the method of claim  1  or supplementing the faecal transplant with one or more bacterial isolates selected from Table 1. 
     
     
         37 . The method of  claim 36  wherein said subject is a healthy subject or cancer patient. 
     
     
         38 . The method of  claim 36  wherein the bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         39 . The method of  claim 36  wherein said method comprises supplementing the faecal transplant with at least 2, 3, 4, 5, 6, 7, 8, 9, 1, 11, 12, 13, 14 or 15 different species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         40 . A method of treating an individual in need of a cancer treatment with an immune checkpoint inhibitor therapy comprising administering to said subject a faecal sample from one or more healthy individual that has been shown to be abundant in one or more of the species in table 1, and/or faecal microbiota from one or several individual(s) treated with an immune checkpoint inhibitor therapy and who proved to respond to this therapy, and/or faecal microbiota from one or several individual(s) exhibiting a gut microbiota profile that identifies the individual(s) as likely to respond to the envisioned treatment or from a responding patient. 
     
     
         41 . The method of  claim 40  wherein immune checkpoint inhibitor inhibits PD-1, PDL-1, PDL-2, TIM-3, TIGIT, LAG-3 or CTLA-4 activity. 
     
     
         42 . The method of  claim 40  wherein bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         43 . The method of  claim 40  wherein the faecal microbiota has been shown to be abundant in least 2, 3, 4, 5, 6, 7, 8, 9, 1, 11, 12, 13, 14 or 15 different species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NOs: 1 to 15. 
     
     
         44 . The method of  claim 40  wherein the cancer is selected from melanoma melanoma, such as Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, acral-lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, nodular melanoma, subungual melanoma, Cutaneous melanoma, uveal/intraocular melanoma and superficial spreading melanoma or bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, brain cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas.